OBJECTIVE: To report a case of immune mediated hemolysis occurring after oxaliplatin infusion in a patient with rectal cancer. CASE SUMMARY: We report a 69 year old male patient who presented with acute onset anemia after infusion of oxaliplatin as chemotherapy. A positive direct Coombs test and good response to steroids treatment underlined the diagnosis of immune related hemolytic anemia. The patient was switched to irinotecan-based chemotherapy regimen for further treatment. DISCUSSION: To our knowledge, there has been less than 10 cases of hemolysis occurring after oxaliplatin treatment in the medical literature. In all cases, immune mediated hemolysis has been proven with a positive coombs test. As oxaliplatin based chemotherapy regimen has become a standardized first line treatment for metastatic colorectal adenocarcinoma, this phenomenon warrants a higher level of physician awareness. CONCLUSIONS: Oxaliplatin related hemolytic anemia is a rare reported phenomenon. Patient under oxaliplatin treatment presenting with sudden hemoglobin decrease should prompt further investigation of hemolysis.